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An array of 60 electrodes on a chip is housed within the white plastic at the chip's center (left). This part of the chip is covered with 60 hydrogel microelectrodes (center). Each is about 3 micrometers in diameter (right).

Biologists studying the electrical activity of the heart and nervous system sometimes face a problem. The tissues they study are soft, but the electrodes used to measure and stimulate the cells are rigid. This mechanical mismatch can stress cells and limits the quality of electrical measurements. Now, researchers have made squishy hydrogel electrodes that match the mechanical properties of living tissues and have shown that they can take better electrical readings from heart and nerve cells (Proc. Natl. Acad. Sci. USA 2018, DOI: 10.1073/pnas.1810827115.

To measure the electrical activity of single cells, biologists often have used flat electrodes or thin wires made of materials like gold or iridium oxide or silicon. The quality of the data they collect is only as good as the interface between the cells and electrodes. The unnatural rigidity of the electrode materials stresses out the cells, leading them to behave abnormally, including changing their gene expression patterns. The material mismatch also prevents the cells from nestling up to the electrode and making strong contact. This physical gap causes impedance, or a muffled and noisy electrical signal. These problems are even more acute when working with moving cardiomyocytes, heart muscle cells that beat even when in a culture dish, says Bianxiao Cui, a materials scientist at Stanford University.

Cui collaborated with Zhenan Bao, also a Stanford materials scientist, to develop an electrode that closely matches the mechanical properties of living tissue. Bao decided to use hydrogels, squishy polymeric materials consisting mostly of water. Other researchers have made conductive hydrogels, but these hydrogels have low conductivity, and it’s difficult to pattern them to make freestanding, pillar-shaped electrodes because they’re full of water.

Credit: Bao/Cui

Each microelectrode starts out as a dry polymer disk. Researchers add buffer, and the disk sprouts into a hydrogel pillar. The electrodes are soft, and can bend and rotate.

To overcome these issues, Bao started with a mix of conductive, stretchy polymers and ionic liquid her lab developed last year (Sci. Adv. 2017, DOI: 10.1126/sciadv.1602076). Organic ions in the mix cause the polymers to aggregate, paving easy paths to conduct electrons. To make arrays of electrodes, the researchers lay down a thin film of the polymer mix atop a chip patterned with electrical contacts. Next, the team dries out the conductive polymer, and uses lithography to carve an array of 60 disks of the polymer at each location on the chip where they want an electrode. Finally, they add a cell-friendly buffer solution and let the disks soak for a few hours. The polymer disks take up the buffer and sprout like seeds, growing straight up from the chip’s surface to form pillars 3 µm in diameter.

The sprouted hydrogel electrodes consist of about 95% water. They are about as conductive as iridium oxide, one of the best-performing conventional electrode materials. The Young’s modulus—a measure of material stretchiness—of the electrodes is 13.4 kilopascals, a tissue-like value. Cardiomyocytes and nerve cells wrapped around the electrodes, and there was less electrical impedance at the electrode-cell interfaces compared with conventional electrodes.

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Cui plans to use the electrodes to characterize the electrical behavior of populations of stem-cell derived cardiomyocytes. Bao says the electrode arrays could be used to take measurements from the heart, or as an interface with the nervous system, for example in smart prosthetic hands equipped with mechanical sensors that relay sensory signals to the wearer.

Bozhi Tian, who develops tools for probing cells’ electrical behavior at the University of Chicago, is eager to try the hydrogel electrodes in his lab. “They are very similar to living tissue, and that will cause less inflammation,” he says. Tian’s also impressed with the quality of the electrical interface between the electrodes and living cells. “This is a major advance,” he says.